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BMP4 signaling plays critical roles in self-renewal of R2i mouse embryonic stem cells

Authors
Taleahmad, SaraSalari, AliSamadian, AzamChae, Se HyunHwang, DaeheeLee, BongheeBayarsaikhan, DelgerBayarsaikhan, GovigerelLee, JaesukPark, Ji HwanHassani, Seyedeh-NafisehBaharvand, HosseinSalekdeh, Ghasem Hosseini
Issue Date
Aug-2022
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
Self-renewal; mESCs; BMP4; Apoptosis; Cell adhesion; RNA-Seq
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.617, pp.8 - 15
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume
617
Start Page
8
End Page
15
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/992
DOI
10.1016/j.bbrc.2022.05.036
ISSN
0006-291X
Abstract
Mouse embryonic stem cells (mESCs) can be maintained in a pluripotent state under R2i culture conditions that inhibit the TGF-I3 and ERK signaling pathways. BMP4 is another member of the TGF-I3 family that plays a crucial role in maintaining the pluripotency state of mESCs. It has been reported that inhibition of BMP4 caused the death of R2i-grown cells. In this study, we used the loss-of-function approach to investigate the role of BMP4 signaling in mESC self-renewal. Inhibition of this pathway with Noggin and dorsomorphin, two bone morphogenetic protein (BMP) antagonists, elicited a quick death of the R2i-grown cells. We showed that the canonical pathway of BMP4 (BMP/SMAD) was dispensable for self-renewal and maintaining pluripotency of these cells. Transcriptome analysis of the BMPi-treated cells revealed that the p53 signaling and two adhesion (AD) and apoptotic mitochondrial change (MT) pathways could be involved in the cell death of the BMPi-treated cells. According to our results, inhibition of BMP4 signaling caused a decrease in cell adhesion and ECM detachment, which triggered anoikis in the R2i-grown cells. Altogether, these findings demonstrate that endogenous BMP signaling is required for the survival of mESCs under the R2i condition.(c) 2022 Published by Elsevier Inc.
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연구본부 (신경·혈관단위체 연구그룹)
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